Easy Access to Functionalized Indolines and Tetrahydroquinolines via a Photochemical Cascade Cyclization Reaction.

Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N-aryl-allylamine and homoallylamine derivatives were reacted with sp3-hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.

Synthesis and structural properties of para-diselenopyrazines.

Recently, dithienopyrazines have emerged as promising building blocks in the field of materials science, showcasing their potential as hole-transport materials in organic electronic devices. Herein, we report the synthesis of its heavier analogues, the diselenopyrazines, along with an analysis of their optoelectronic and structural properties. In the acquired crystal structures, interesting molecular packing motifs suitable for potential device fabrication were observed. Additionally, short contact interactions are present in one of the investigated molecules.

Gold(I)-Catalyzed Intramolecular 7-endo-dig Cyclization of Triene-Yne Systems: New Access towards Azulenothiophenes.

We report the direct synthesis of new azulene derivatives through gold-catalyzed cyclization reactions. A five-membered ring as backbone in the applied triene-yne substrates turned out to be crucial to induce the 7-endo-dig cyclization mode necessary to trigger azulene formation. The obtained targets are of high interest due to their potential applications in different fields, like organic materials, medicine or cosmetics. UV/Vis spectra and cyclic voltammetry were measured, based on these the electronic properties were determined. Short two or three step sequences towards the applied starting materials make this approach synthetically highly attractive.

Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes.

Inorganic pyrophosphate is a key molecule in many biological processes from DNA synthesis to cell metabolism. Here we introduce sp3-functionalized (6,5) single-walled carbon nanotubes (SWNTs) with red-shifted defect emission as near-infrared luminescent probes for the optical detection and quantification of inorganic pyrophosphate. The sensing scheme is based on the immobilization of Cu2+ ions on the SWNT surface promoted by coordination to covalently attached aryl alkyne groups and a triazole complex. The presence of Cu2+ ions on the SWNT surface causes fluorescence quenching via photoinduced electron transfer, which is reversed by copper-complexing analytes such as pyrophosphate. The differences in the fluorescence response of sp3-defect to pristine nanotube emission enables reproducible ratiometric measurements in a wide concentration window. Biocompatible, phospholipid-polyethylene glycol-coated SWNTs with such sp3 defects are employed for the detection of pyrophosphate in cell lysate and for monitoring the progress of DNA synthesis in a polymerase chain reaction. This robust ratiometric and near-infrared luminescent probe for pyrophosphate may serve as a starting point for the rational design of nanotube-based biosensors.

Cascade Reactions of Aryl-Substituted Terminal Alkynes Involving in Situ-Generated α-Imino Gold Carbenes.

An efficient, highly selective and divergent synthetic method to construct 2-substituted indoles and aryl-annulated carbazoles via the intermolecular generation of α-imino gold carbenes from terminal alkynes or diynes in combination with sulfilimines is disclosed. Importantly, the tandem reaction is proposed to proceed through an intermolecular gold carbene generation/C-H annulation followed by the activation of a second alkyne leading to 6-endo-dig cyclization, which is significantly different from previous dual activation or 1,6-carbene shift approaches for diyne systems. In the case of ortho-alkynylaniline as starting material, an unexpected regioselective formation of the indole moiety via the intermolecular path, instead of intramolecular hydroamination was discovered. This reactivity paved the way for a one-pot synthesis of the 11H-indolo [3,2-c] quinoline scaffold by exploiting the formed amino indole for a subsequent Pictet-Spengler reaction with aldehydes. The photophysical properties of the carbazoles indicated good violet-blue emission with quantum yields up to 40 %.

Ameliorative effects of Lactobacillus against Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P 0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p 0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Ameliorative effects of Lactobacillus against Aflatoxin B1 / Efeitos benéficos do Lactobacillus contra a Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P<0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p<0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P < 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p < 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Mn(III) O

Polyurethanes are synthesized on industrial scale by the reaction of diisocyanates with diols in the presence of catalysts which are commonly based on tin complexes and amines. However, due to the toxicity and volatility of these tin catalysts and amines, there is the need to develop new catalysts that are more environmentally benign. Herein, we report the synthesis of O^N^O pincer-ligated Mn(III) and Fe(III) complexes that serve as suitable catalysts for urethane formation and are stable to hydrolysis as predicted by computations and observed experimentally. The O^N^O pincer scaffold is vital to the activity of these catalysts, simultaneously ensuring increased solubility in the reaction medium as well as providing a stable framework upon dissociation of co-ligands in the catalytic cycle. In silico mechanistic investigations for urethane formation show that the stabilization of active species in square-planar geometries enabled by these O^N^O ligands permit the simultaneous coordination of alcohol and isocyanate in suitable configuration at the metal center.

Light-Induced Metal-Free Generation of Cyanocarbenes from Alkynyl Triazenes for the Synthesis of Nitrile Derivatives.

The chemistry of alkynyl triazenes is an emerging field for organic chemists and especially acid-induced nucleophilic functionalizations, either directly, or after a prior reaction towards aromatic triazenes under extrusion of nitrogen, paved the way for fruitful strategies. In contrast, the chemical behavior of alkynyl triazenes upon irradiation with light is still unknown. Herein we present the first photoactivation of alkynyl triazenes that triggers an uncommon reactivity pattern involving the cleavage of the N1-N2 bond of the triazene moiety resulting in a unique approach to cyanocarbenes from a readily available, stable, and insensitive precursor. This allows to access various nitrile compounds without the use of a toxic cyanating agent by exploiting the reactivity pattern of carbenes. By variation of the reaction conditions and light sources, different substitution patterns can be obtained selectively in good yields under mild and metal-free conditions, thus introducing the alkynyl triazene unit as a photo accessible methylene nitrile synthon. Using this synthon, subclasses like α-alkoxynitriles, α-aminonitriles and α-cyanohydrazones become easily available. These exhibit synthetically valuable substitution patterns for the synthesis of pharmaceuticals, intermediates for total synthesis and amino acid synthesis.

Gold(I)-Mediated Cyclizations of Triene-Yne Systems: An Easy Access to Cyclopenta-Fused Anthracenes.

The direct synthesis of cyclopenta-fused anthracenes (CP-anthracenes) through a gold(I)-catalyzed cyclization reaction of easily available triene-yne systems bearing a benzofulvene substructure, is reported. The targets are of great interest due to the potential use as organic materials and the preparation of these compounds is gaining huge importance. The applied starting materials are readily available through a three-step synthesis, which further contributes to the advantages of this route. In addition, UV-Vis and fluorescent spectra of the obtained CP-anthracenes were recorded.

Gold-Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor-Active Spirocyclic Oxindoles from Alkynes and Isatin-Derived Ketimines.

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones.

Gold-Catalyzed [3,3]-Sigmatropic Rearrangement of ortho-Alkynyl-S,S-diarylsulfilimines.

Highly functionalized 5H-pyrrolo[2,3-b]pyrazine cores, carrying a diaryl sulfide moiety at the C-7 position, were obtained from a gold-catalyzed reaction using easily accessible ortho-alkynyl-substituted S,S-diarylsulfilimines as intramolecular nitrene transfer reagents for the first time. The reaction proceeds under mild conditions, providing excellent yields while tolerating a large variety of different substitution patterns. We provide experimental evidence for an intramolecular reaction mechanism, likely including an unprecedented gold-catalyzed amino sulfonium [3,3]-sigmatropic rearrangement.

Gold-Catalyzed Regio- and Stereoselective α-Acyloxy-ß-Alkynylation of Ynol Ethers.

Enol esters and conjugated enynes are valuable structural motifs for synthetic chemistry and material sciences. Herein, the synthesis of tetra-substituted enol ester 2-iodobenzoate derivatives was achieved in good yields at room temperature through a gold-catalyzed acyloxyalkynylation of sensitive ynol ethers with ethynylbenziodoxolones (EBXs), the latter acting as bifunctional reactants. The conversion is highly regioselective with a broad substrate scope. Mechanistically, an Au(III) species is the key intermediate of an Au(I)/Au(III) redox cycle. The reaction is synthetically useful and can easily be scaled up to gram scale.

An unexpected synthesis of azepinone derivatives through a metal-free photochemical cascade reaction.

Azepinone derivatives are privileged in organic synthesis and pharmaceuticals. Synthetic approaches to these frameworks are limited to complex substrates, strong bases, high power UV light or noble metal catalysis. We herein report a mild synthesis of azepinone derivatives by a photochemical generation of 2-aryloxyaryl nitrene, [2 + 1] annulation, ring expansion/water addition cascade reaction without using any metal catalyst. Among the different nitrene precursors tested, 2-aryloxyaryl azides performed best under blue light irradiation and Brønsted acid catalysis. The reaction scope is broad and the obtained products underwent divergent transformations to afford other related compounds. A computational study suggests a pathway involving a step-wise aziridine formation, followed by a ring-expansion to the seven-membered heterocycle. Finally, water is added in a regio-selective manner, this is accelerated by the added TsOH.

On the Role of Noncovalent Ligand-Substrate Interactions in Au(I) Catalysis: An Experimental and Computational Study of Protodeauration.

A systematic study of protodeauration, a crucial step often found in gold catalysis, was performed using isolated vinyl gold(I) complexes. By varying substituents on gold complexes, we explore how their properties influence protodeauration. Phenols were employed as the proton source, and their substituents were also varied, providing insight through variation of their acidity. A linear Hammett correlation is identified for the series of substituted vinyl gold(I) complexes, while a nonlinear trend is found for the series of substituted phenols. Computationally, we reproduce our experimental observations and identify significant noncovalent interactions (NCIs) between the proton donor and vinyl gold(I) complexes. This finding is of particular importance for gold-catalyzed reactions as they often employ linear two-coordinate complexes where the site of the reaction is spatially remote from the ligand bound to gold. The NCIs between substrates and intermediates lead to a significant acceleration of the protodeauration step in this work, opening the door to alternative strategies in the field of gold catalysis.

Synthesis of Amide Enol 2-Iodobenzoates by the Regio- and Stereoselective Gold-Catalyzed Acyloxyalkynylation of Ynamides with Hypervalent Iodine Reagents.

Multisubstituted alkenes are accessible by a gold-catalyzed acyloxyalkynylation of ynamides with ethynylbenziodoxolones (EBXs) with perfect atom-economy. The EBX reagents transfer both the carboxylate as well as the alkynyl entity. Overall, this cascade comprises the in situ generation of an alkynyl gold(III) species, a stereoselective C(sp)-C(sp2) bond formation, and a C-O coupling at the alkynyl position of the ynamides. This reaction proceeds under mild conditions and accepts a wide range of substrates. A number of tetrasubstituted amide enol 2-iodobenzoates bearing different functional groups were obtained in good to excellent yields. DFT calculations explain the observed regioselectivity. The synthetic potential of the reaction was further demonstrated by a number of selected follow-up transformations.

Substituted Cyclopentannulated Tetraazapentacenes.

Brominated pentannulated dihydrotetraazapentacenes were prepared by gold- or palladium-catalyzed 5-endo-dig cyclization of TIPS-ethynylated dihydrotetraazaacenes (TIPS = triisopropylsilyl). Post-functionalization was demonstrated by Sonogashira alkynylation and Rosenmund-von Braun cyanation. Calculations predict these species to act as n-type semiconductors, which was verified for two derivates through characterization in organic field-effect transistors.

Synthesis of α-Ketoamides via Gold(I) Carbene Intermediates.

α-Ketoamides have been found to be an important functional group in a broad spectrum of inhibitors such as the Corona virus and other viruses. Here we report an unprecedented gold-catalyzed 2-fold reaction of a bromoalkyne with anthranils. Hydrolysis of the initial product then directly leads to α-ketoamides. Water addition to the intermediate α-iminoimidoyl halides delivered α-ketoamides from a broad range of bromoalkynes.

Entropy-Induced Selectivity Switch in Gold Catalysis: Fast Access to Indolo[1,2-a]quinolines.

New N-heterocyclic compounds for organic functional materials and their efficient syntheses are highly demanded. A surprising entropy-induced selectivity switch in the gold-catalyzed intramolecular hydroarylation of 2-ethynyl N-aryl indoles was found and its exploitation led to straightforward syntheses of indolo[1,2-a]quinolines. Experimental and computational mechanistic investigations gave insight into this uncommon selectivity phenomenon and into the special reactivity of the indolo[1,2-a]quinolines. The high functional group tolerance of this methodology enabled access to a diverse scope with high yields. In addition, bidirectional approaches, post-functionalization reactions, and π-extension of the core structure were feasible. An in-depth study of the photophysical properties explored the structure-effect relationship for different derivatives and revealed a high potential of these compounds for future applications as functional materials.